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Letter from William Castle to Linus Pauling. November 29, 1946.
Castle writes to thank Pauling for his letter and to discuss sickle cell research in greater depth. In so doing, Castle notes that the literature is full of publications indicating that oxygen and carbon monoxide prevent blood sickling, and provides greater details about his own work in determining the oxygen tension necessary to initiate sickling. Castle closes by indicating that his future research interests include measuring sickling as a function of blood viscosity.





November 25, 1946

Dr. Linus Pauling

Gates and Crellin Laboratories of Chemistry

California Institute of Technology

Pasadena 4, California

Dear Linus:

How nice it is to have a word from you and probably to learn something more as a result of your work about that most interesting condition, sickle cell anemia. With regard to the facts about sickling, it is well established that oxygen and carbon monoxide prevent sickling, and that exposure to other gases produce sickling by the removal of one or the other of these. Naturally, there is some effect from carbon dioxide in so far as it alters the saturation curve for oxygen of the hemoglobin by a change in the pH of the system. I would agree with you that Doctor Burch's papers can all be interpreted in terms of removal of oxygen and, indeed, I wrote a critique of one of them for the Year Book of Medicine in which I simply interpolated the abstract of his communication in terms of this explanation.

I think that the literature that would be most useful for you, both for its content and for the references given, is the following:

Scriver, J. B., and Waugh, T. R. Canad. Med. Assn. J. 1930, 23, 375-380.

Murphy, R. C., and Shapiro, S. Arch. Int. Med., 1944, 74, 28. (Cf. Bibliography)

Same authors, Annals Int. Med. 1945, 23, 376. (Cf. Bibliography)

Our own observations here confirm those of Scriver and Waugh that sickling begins at about 35 to 40 millimeters oxygen tension. We were interested to determine the sickling by the effect on the "viscosity"; that is, the timed flow of blood through a viscosimeter with appropriate arrangements to maintain the blood in equilibrium with various tensions of oxygen. The viscosity of the blood begins to increase at about 40 millimeters oxygen tension, and rises

Dr. Linus Pauling, November 25, 1946—2

sharply in the range between 20 and 40. As you know, the tension of the capillary blood is in this range, and consequently the sickling phenomenon probably is the basis of the rather uniform and striking pathology of sickle cell disease. We have published only a sentence or two on this topic, but, as far as I know, it is the first observation of the "viscosity" of the blood. The reference is:

Ham, T. H. and Castle, W. B. Tr. Assn. Am. Phys., 1940, 55, 127.

I hope this is the information you want. It would be pleasant to see you sometime, and in the meantime I send all best regards to you.

Sincerely yours,

William B, Castle, M.D.


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